Retinaldehyde-binding protein 1 (RLBP1) also known as cellular retinaldehyde-binding protein (CRALBP) is a 36-kD water-soluble

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''RLBP1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Discovery

Cellular

retinol binding protein Retinol-binding proteins (RBP) are a family of proteins with diverse functions. They are carrier proteins that bind retinol. Assessment of retinol-binding protein is used to determine visceral protein mass in health-related nutritional studies. R ...

(CRBP) was first discovered in 1973 from lung tissues by Bashor et al. There have been three cellular

categories discovered; Cellular retinol-binding protein, cellular retinoic acid-binding protein and cellular retinaldehyde-binding protein(CRALBP). CRALBP was first discovered in 1977, after it was purified from retina and retinal pigment epithelial cells.

Function

The cellular retinaldehyde-binding protein transports 11-cis-retinal (also known as 11-cis-retinaldehyde) as its physiological ligands. It plays a critical role as an 11-cis-retinal acceptor which facilitates the

enzymatic Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

isomerization In chemistry, isomerization or isomerisation is the process in which a molecule, polyatomic ion or molecular fragment is transformed into an isomer with a different chemical structure. Enolization is an example of isomerization, as is tautomeriz ...

of all 11-trans-retinal to 11-cis-retinal, in the isomerization of the rod and

cones A cone is a three-dimensional geometric shape that tapers smoothly from a flat base (frequently, though not necessarily, circular) to a point called the apex or vertex. A cone is formed by a set of line segments, half-lines, or lines conn ...

of the visual cycle.

Tissue distribution

CRALBP is not just found in retina and retinal pigment epithelial cells, but also expressed in other cell types. It is majorly found in the

iris Iris most often refers to: *Iris (anatomy), part of the eye *Iris (mythology), a Greek goddess * ''Iris'' (plant), a genus of flowering plants *Iris (color), an ambiguous color term Iris or IRIS may also refer to: Arts and media Fictional enti ...

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...

, ciliary epithelium,

Muller Muller is a surname. Notable people with the surname include: A–H * A. Charles Muller (born 1953), translator *Bauke Muller (born 1962), Dutch bridge player *Bennie Muller (born 1938), Dutch footballer *Bill Muller (1965–2007), US journalist ...

cells, the

pineal gland The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep, sleep patterns in both circadian rhythm, circ ...

and

oligodendrocyte Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of jawed vertebrates, equivalent to the function performed by Schwann cells in the ...

s of the optic

nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...

and brain. This protein is also found in other tissues than the aforementioned ones, however its function in cells not related to the eyes are not yet known

Clinical significance

When a visual pigment molecule in photoreceptors of mammalian rod and cone cells are triggered by photons of light, the pigment molecule is unable to detect an ensuing photon of light. All the retinal molecules in the

chromophore A chromophore is the part of a molecule responsible for its color. The color that is seen by our eyes is the one not absorbed by the reflecting object within a certain wavelength spectrum of visible light. The chromophore is a region in the molec ...

of the visual pigment molecule, exist in the 11-trans-retinal state after stimulation by photons. RLBP1 helps in converting the 11-trans-retinal to the light sensitive 11-''cis'' retinal. This process is a part of the visual cycle, which involves the expulsion of all 11-trans-retinal containing chromophores out of photoreceptors, and subsequent conversion to the 11-cis-retinal state in retinal pigment epithelial cells, for both rod and cone cells. The 11-cis chromophore is then signalled back into photoreceptor cells, where it undergoes fusion with a free opsin molecule to regenerate the visual pigment.

Gene location

The RLBP1

is located on human chromosome 15, specifically on 15q26. This gene was formerly believed to have 8

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s and 7

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...

s. However, Vogel et al. demonstrated that there are actually 8 introns on that chromosome. A gene element,

upstream Upstream may refer to: * Upstream (bioprocess) * ''Upstream'' (film), a 1927 film by John Ford * Upstream (networking) * ''Upstream'' (newspaper), a newspaper covering the oil and gas industry * Upstream (petroleum industry) * Upstream (software ...

of the previously thought exon 1 was originally thought to be an enhancer. In reality, this assumed enhancer is the main promoter for this gene. The newly discovered intron 1 lies within and just near the end of the promoter region of RLBP1 gene.

Mutations and associated diseases

Mutations of RLBP1 include several diseases associated with vision. All of these are

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

including Bothnia dystrophy, retinitis punctata albescens,

retinitis pigmentosa Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...

, Newfoundland rod-cone dystrophy and fundus albipunctatus. The characteristics of the associated diseases vary with age, severity and rate of progression. These all have similar qualities such as, photoreceptor deterioration and slower dark adaptation, ultimately leading to

visual impairment Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment� ...

, often leading to complete blindness.

Bothnia dystrophy

People suffering from Bothnia dystrophy have a

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

C to T base pair substitution in exon 7 of the RLBP1 gene. This leads to a

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense m ...

from Arginine to Tryptophan at the 234 position of the RLBP1.

Retinitis punctata albescens and fundus albipunctatus

Katsanis et al. showed that a homozygous alteration from Arginine to Glutamine amino acid expression, at the 150 position on RLBP1, brings about the onset of retinitis punctata albescens and or fundus albipunctatus.

References

External links

GeneReviews/NIH/NCBI/UW entry on Retinitis Pigmentosa Overview